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Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants

PTEN is a major tumor suppressor gene frequently mutated in human tumors, and germline PTEN gene mutations are the molecular diagnostic of PTEN Hamartoma Tumor Syndrome (PHTS), a heterogeneous disorder that manifests with multiple hamartomas, cancer predisposition, and neurodevelopmental alterations...

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Autores principales: Torices, Leire, Nunes-Xavier, Caroline E., López, José I., Pulido, Rafael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393154/
https://www.ncbi.nlm.nih.gov/pubmed/37527256
http://dx.doi.org/10.1371/journal.pone.0289369
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author Torices, Leire
Nunes-Xavier, Caroline E.
López, José I.
Pulido, Rafael
author_facet Torices, Leire
Nunes-Xavier, Caroline E.
López, José I.
Pulido, Rafael
author_sort Torices, Leire
collection PubMed
description PTEN is a major tumor suppressor gene frequently mutated in human tumors, and germline PTEN gene mutations are the molecular diagnostic of PTEN Hamartoma Tumor Syndrome (PHTS), a heterogeneous disorder that manifests with multiple hamartomas, cancer predisposition, and neurodevelopmental alterations. A diversity of translational and splicing PTEN isoforms exist, as well as PTEN C-terminal truncated variants generated by disease-associated nonsense mutations. However, most of the available anti-PTEN monoclonal antibodies (mAb) recognize epitopes at the PTEN C-terminal tail, which may introduce a bias in the analysis of the expression of PTEN isoforms and variants. We here describe the generation and precise characterization of anti-PTEN mAb recognizing the PTEN C2-domain, and their use to monitor the expression and function of PTEN isoforms and PTEN missense and nonsense mutations associated to disease. These anti-PTEN C2 domain mAb are suitable to study the pathogenicity of PTEN C-terminal truncations that retain stability and function but have lost the PTEN C-terminal epitopes. The use of well-defined anti-PTEN mAb recognizing distinct PTEN regions, as the ones here described, will help to understand the deleterious effects of specific PTEN mutations in human disease.
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spelling pubmed-103931542023-08-02 Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants Torices, Leire Nunes-Xavier, Caroline E. López, José I. Pulido, Rafael PLoS One Research Article PTEN is a major tumor suppressor gene frequently mutated in human tumors, and germline PTEN gene mutations are the molecular diagnostic of PTEN Hamartoma Tumor Syndrome (PHTS), a heterogeneous disorder that manifests with multiple hamartomas, cancer predisposition, and neurodevelopmental alterations. A diversity of translational and splicing PTEN isoforms exist, as well as PTEN C-terminal truncated variants generated by disease-associated nonsense mutations. However, most of the available anti-PTEN monoclonal antibodies (mAb) recognize epitopes at the PTEN C-terminal tail, which may introduce a bias in the analysis of the expression of PTEN isoforms and variants. We here describe the generation and precise characterization of anti-PTEN mAb recognizing the PTEN C2-domain, and their use to monitor the expression and function of PTEN isoforms and PTEN missense and nonsense mutations associated to disease. These anti-PTEN C2 domain mAb are suitable to study the pathogenicity of PTEN C-terminal truncations that retain stability and function but have lost the PTEN C-terminal epitopes. The use of well-defined anti-PTEN mAb recognizing distinct PTEN regions, as the ones here described, will help to understand the deleterious effects of specific PTEN mutations in human disease. Public Library of Science 2023-08-01 /pmc/articles/PMC10393154/ /pubmed/37527256 http://dx.doi.org/10.1371/journal.pone.0289369 Text en © 2023 Torices et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Torices, Leire
Nunes-Xavier, Caroline E.
López, José I.
Pulido, Rafael
Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
title Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
title_full Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
title_fullStr Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
title_full_unstemmed Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
title_short Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants
title_sort novel anti-pten c2 domain monoclonal antibodies to analyse the expression and function of pten isoform variants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393154/
https://www.ncbi.nlm.nih.gov/pubmed/37527256
http://dx.doi.org/10.1371/journal.pone.0289369
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